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Colorectal Cancer Cell Surface Protein Profiling Using an Antibody Microarray and Fluorescence Multiplexing
Published on: September 25, 2011
Mapping the cancer surface proteome in search of target antigens for immunotherapy
Francesco Di Meo1, Brandon Kale1, John M Koomen2
1Department of Blood and Marrow Transplant and Cellular Immunotherapy, Tampa, FL, USA.
Abstract:
Immune-based therapeutic interventions recognizing proteins localized on the cell surface of cancer cells are emerging as a promising cancer treatment. Antibody-based therapies and engineered T cells are now approved by the Food and Drug Administration to treat some malignancies. These therapies utilize a few cell surface proteins highly expressed on cancer cells to release the negative regulation of immune activation that limits antitumor responses (e.g., PD-1, PD-L1, CTLA4) or to redirect the T cell specificity toward blood cancer cells (e.g., CD19 and B cell maturation antigen). One limitation preventing broader application of these novel therapeutic strategies to all cancer types is the lack of suitable target antigens for all indications owing in part to the challenges in identifying such targets. Ideal target antigens are cell surface proteins highly expressed on malignant cells and absent in healthy tissues. Technological advances in mass spectrometry, enrichment protocols, and computational tools for cell surface protein isolation and annotation have recently enabled comprehensive analyses of the cancer cell surface proteome, from which novel immunotherapeutic target antigens may emerge. Here, we review the most recent progress in this field.
Insights
Immune-based cancer therapies show promise but are limited by the lack of suitable cell surface targets. Recent technological advances enable comprehensive proteome analysis to discover new targets for broader cancer treatment.
Area of Science:
- Oncology
- Immunology
- Proteomics
Background:
- Immune-based therapies, including antibody treatments and engineered T-cells, are FDA-approved for certain cancers.
- These therapies target cell surface proteins (e.g., PD-1, CD19) to enhance anti-tumor responses or redirect T-cell specificity.
- A key limitation is the scarcity of suitable cell surface target antigens across all cancer types.
Purpose of the Study:
- To review recent advancements in identifying novel cancer cell surface targets for immunotherapy.
- To highlight the potential of comprehensive cancer cell surface proteome analysis.
Main Methods:
- Leveraging technological advances in mass spectrometry for cell surface protein isolation.
- Utilizing advanced enrichment protocols and computational tools for proteome annotation.
- Comprehensive analysis of the cancer cell surface proteome.
Main Results:
- Emerging technologies facilitate detailed analysis of cancer cell surface proteins.
- This enables the identification of potential novel immunotherapeutic targets.
- Progress in the field is rapidly expanding the landscape of potential targets.
Conclusions:
- Discovering ideal cell surface antigens (highly expressed on cancer, absent in healthy tissue) is crucial for broader immunotherapy application.
- Technological progress in proteomic analysis is key to overcoming current limitations.
- This field holds significant promise for developing new cancer treatments.
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